CD4 enhances T cell sensitivity to antigen by coordinating Lck accumulation at the immunological synapse.
Journal Article (Journal Article)
How T cells respond with extraordinary sensitivity to minute amounts of agonist peptide and major histocompatibility complex (pMHC) molecules on the surface of antigen-presenting cells bearing large numbers of endogenous pMHC molecules is not understood. Here we present evidence that CD4 affects the responsiveness of T helper cells by controlling spatial localization of the tyrosine kinase Lck in the synapse. This finding, as well as further in silico and in vitro experiments, led us to develop a molecular model in which endogenous and agonist pMHC molecules act cooperatively to amplify T cell receptor signaling. At the same time, activation due to endogenous pMHC molecules alone is inhibited. A key feature is that the binding of agonist pMHC molecules to the T cell receptor results in CD4-mediated spatial localization of Lck, which in turn enables endogenous pMHC molecules to trigger many T cell receptors. We also discuss broader implications for T cell biology, including thymic selection, diversity of the repertoire of self pMHC molecules and serial triggering.
Full Text
Duke Authors
Cited Authors
- Li, Q-J; Dinner, AR; Qi, S; Irvine, DJ; Huppa, JB; Davis, MM; Chakraborty, AK
Published Date
- August 2004
Published In
Volume / Issue
- 5 / 8
Start / End Page
- 791 - 799
PubMed ID
- 15247914
International Standard Serial Number (ISSN)
- 1529-2908
Digital Object Identifier (DOI)
- 10.1038/ni1095
Language
- eng
Conference Location
- United States